PROJECT SUMMARY/ ABSTRACT Pre-exposure prophylaxis (PrEP) is a promising bio-medical HIV prevention strategy that involves the use of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) by HIV negative individuals to reduce their risk of acquiring HIV. Evidence suggests women who inject drugs (WWID) are disproportionately vulnerable to HIV. While PrEP could significantly reduce HIV acquisition among WWID, at present, there is little knowledge to help address PrEP implementation challenges for this understudied group. The proposed study will address our knowledge gap about PrEP by evaluating a novel approach for the delivery of PrEP care, namely, packaging PrEP and testing and treatment for sexually transmitted infections with community-based syringe exchange program (SEPs) services. The rationale is that (1) SEPs may currently provide prescription medications and long-term monitoring for other conditions such as buprenorphine for opioid dependence, so providing PrEP care is a natural extension of what is already being done successfully; (2) SEPs are a viable access point for many HIV-uninfected WWID who would be considered eligible for PrEP under current clinical guidelines; and (3) PrEP interventions, delivered in settings already utilized and trusted by WWID, will increase uptake, adherence and retention in PrEP. Packaging PrEP care at a syringe exchange program is highly innovative. To our knowledge, this approach has not been tested and may represent a paradigm shift that enables and encourages women in this highly vulnerable population to engage in effective biomedical HIV prevention strategies. To evaluate the impact of this approach, we will initiate a prospective mixed methods study with primary and secondary syringe exchange users. Through semi-structured and in-depth interviews based on the Behavioral Model for Vulnerable Populations, and drug-level monitoring for FTC, we will address the following specific aims: (1) Describe WWID's engagement in the PrEP care continuum (focusing on critical moments when women could disengage or need additional support to remain in care). (2) Assess the impact of predisposing, enabling, and need-related factors on WWID's engagement in the PrEP care continuum. (3) Explore how and why model factors are associated with WWID's decisions and ability to engage in PrEP care. Unless new clinic-independent intervention methods are developed to target the specific barriers to PrEP found among WWID, engagement in this group is likely to remain suboptimal. The reproducibility of this approach significantly increases this work's potential for translation to other settings. The long term-impact will be a reduction in HIV and improved health outcomes of WWID through the delivery of combination HIV prevention interventions that include PrEP.